Preparation of p-(nu-primary aliphatic amino) phenols



Patented Jul 15, 1941 UNITED STAT PREPARATION OF r-m rnnwmx ALI- PHATIC ammo) PHENOLS Howard Montgomery Fitch, Wilmington, Dei., assignor to E. I. do Pont de Nemours & Company, Wilmington, Del., a corporation or Delaware No Drawing.

21 Claims.

This invention relates to the preparation of p-(N-primary aliphatic amino) phenols and particularly from p-nitrophenols and p-nitrosophenols.

Many attempts have been made to produce N-alkyl aminophenols by first condensing normal aliphatic aldehydes, such as acetaldehyde and n-butyraldehyde, with primary aminophenols to produce the corresponding N-alkylidene aminophenols and subsequently hydrogenating the N-alkylidene aminophenols. Generally these processes have not proved to.be commercially successful for the reason that the reaction products formed by the condensation of the aidehydes with the aminophenols have usually been amorphous or tarry products of indefinite con stitution, which do not reduce cleanly to N-alkyl aminophenols. Recently I have discovered a method of preparing N-monoaliiyl amlnophenols from aldehydes and aminophenols, which method has proved to be commercially successful and to be free of many of the objectionable features of the previously proposed processes. Such newly discoveredmethod is disclosed and claimed in my copending application, Serial No. 245,911, filed December 15, 1938. Such methods have involved the use and handling of p-aminophenols which are unstable, dliiicult to refine and handle, and relatively expensive.

R. T. Major in the Journal of the American 30 Chemical Society, 53, 1901 and 2803 (1931) has proposed the preparation of N-substituted aminophenols from p-nitrophenols. He was apparently successful in preparing N-secondary alkyl aminophenols by reducing p-nitrophenol in the presence of ketones. He indicates that a hydroxylamine is formed as an intermediate and reacts with the keton'e-to form the alkyl aminophenol. Major also indicates that aromatic aldehydes,

such as benzaldehyde, will react somewhat- Application February 23, 1940, Serial No. 320,417

(oi. zoo- 57s) phenols and p-nitrosophenols in a single step which does not require the isolation and purification of intermediate products. Other objects are to advance the art. Still other objects will appear hereinafter.

The above and other objects may be accomplished in accordance with my invention, which comprises reducing a p-nitrophenol or a p-hitrosophenol in the presence of an aliphatic aldehyde containing at least 3 carbon atoms, preferably -employing from about 1 to about 1.5 molecular proportions of the aldehyde for each mol of the p-nitrophenol or p-nitrosophenol, whereupon, p-(N-primary aliphatic amino) phenols are obl5 tained in high yields and in a high state of purity.

By the term "aliphatic," aldehydes and the like,

., I mean the strictly aliphatic compounds or groups and to exclude aldehydes and the like containing aromatic rings. The aliphatic aldehydes employed may contain hydroxyl, halogen and alkoxy. groups, but are preferably unsubstituted. By the term unsubstituted aliphatic aldehydes, I mean to include both saturated and unsaturated aldehydes that, except for the oxygen of the aldehyde group, consist of carbon and hydrogen. Of the unsubstituted aliphatic aldehydes, I preferably employ the alkyl aldehydes. By the term "alkyl aldehydes," I intend to include only the saturated aliphatic aldehydes that, except for the oxygen of the aldehyde group, consist of carbon and hydrogen. Amongst the aldehydes that may be employed in my process are:

The p-nitrophenols and p-nitrosophenols, which may be employed in accordance with my 55 invention, may contain, as substituents, alkyl,

aryl, aralhl, alkoxy, aralkoxy, amino, halogen and additional hydroxyl and ultra group but trosophenols, or, in other words, the p-nitrophenols and p-nitrosophenols that are devoid of non-hydrocarbon substituents.

The reaction is preferably carried out in the liquid phase and in the presence of an inert solvent. By an inert solvent, I mean one which is inert to the initial reacting materials and to the N-aliphatic aminophenols. Although non polar solvents, such as benzene, toluene, chlorobenzene, cetane, and the like, may be employed as suitable solvents, polar solvents are preferred. By the term "polar solvent" is meant solvents selected from aliphatic alcohols, esters derived from aliphatic alcohols and aliphatic acids, aliphatic ethers, alcohol .ethers, halogenated aliphatic hydrocarbons, water and mixtures of two or more thereof. Examples of suitable polar solvents are methanol, ethanol, butanol, isobutanol, ethyl acetate, isopropyl ether, dioxane, methyl cellosolve, and ethylene dichloride. Also mixturesof polar and non-polar solvents may be employed. The alcohols will generally be preferred and particularly mixtures thereof with water, such as 95% alcohol. I

It will be found practical to employ from about 1 to about 1.5 mols of aldehyde for each mol of p-nitrophenoi or p-nitrosophenol. Larger or smaller amounts of aldehyde may be employed,. but without substantial advantage. A lesser amount of aldehyde will necessarily leave unreacted p-nitrophenol, p-nitrosophenol, or paminophenol, depending upon the conditions of 2 amassa in such a way that its position is more or less permanent.

Amongst the catalysts which may be employed, the noble metal catalysts, such as platinum oxide, palladium oxide, platinum chlorides and palladium chlorides, are particularlysuitable. An

- However; other catalysts, particularly of the iron group, such as .active iron or cobalt, may be em ployed. If desired, the catalyst may be in the form ofia metallic wool or screen. The catalyst may'alternatively comprise a salt of a hydrogenating metal, such as, for example, cobalt, copper, iron, silver or nickel, employed with a promoting oxide. A representative catalyst of this latter type is copper chromite, which may be used in place of nickel, either with or without previous reduction.

The temperatures and pressures of hydrogenation are subject to considerable variation, depending upon the nature of the aldehydes, the solvents and the catalysts. The temperatures may range from as low as 0 C. to about 200 C. Generally, temperatures from about atmospheric to about 200 C. will be employed. When a catalyst is employed, .I particularly prefer to employ temperatures from about 75 C. to about 150 C. When a noble metal catalyst is employed, the hydrogenation may be readily accomplished at pressures of from about 2 toabout'3 atmospheres. When a base metal catalyst is employed, temperatures of from about 75 C. to about 150 C. and pressures of from about 10 to about 100 atmospheres will generally be preferred. With either type of catalyst, temperatures ashigh as 200 C.

and pressures as high as 2000 pounds per square reduction, to be separated from the desired prod uct. Too large an amount of aldehyde tends to give by-products such as the p-(N-di-primary aliphatic amino) phenols. Furthermore, any excess of aldehyde may be reduced to the corresponding alcohol during the hydrogenation, involving the waste of valuable aldehyde; but preferabLv aslight excess of the aldehyde is employed in carrying out the reaction, and particularly from about 1.2 to about 1.5 mols are employed for each mol of the p-nitrophenol or p-nitrosophenol.

While the reduction or hydrogenation may be accomplished by chemical means, such as with zinc and caustic alkali, or with activated aluminum and caustic alkali, the preferred method ofplete the reduction may be diminished by adding the catalyst gradually or step-wise to the reaction mixture during the course of the reduction. In this modification of the process,.the catalyst may be added dry or suspended or dispersed in the liquid. The catalyst, whether or not it is added prior to or during the reduction process,

may be supported on a suitable support such. as.. for example, kieselguhr, carborundum, or the like. The catalyst may be distributed throughout the reaction mixture or fixed on a carrier inch or higher maybe used. The particular temperatures and pressures employed will depend to a large extent upon the desire of the operator and the equipment available. The temperatures and pressures of operation should preferably be so regulated that the solvent employed is not materially hydrogenated.

The reaction may be carried out by first mixing the aldehyde and the p-nitrophenol .or the p-nitrosophenol and then subjecting the mixture to hydrogenation conditions. However, it is preferable to add all or part of the aldehyde to the p-nitrophenol or p-nitros'ophenol gradually or step-wise during the course of the hydrogenation. The addition of the aldehyde gradually during the hydrogenation is particularly desirable when readily polymerizable aldehydes, such as the normal saturated aldehydes, are employed. The aldehydes may be added as such, dissolved in a solvent, or dispersed in a suitable liquid medium.

In order to illustrate my invention more clearly, the preferred modes of carrying the same into eifect and the advantageous results to be obtained thereby, the following examples are given:

Emu: 1

lV-propyl-p-aminophevwl A mixture of 58 parts of p-nitrophenol (0.4 mol) 31 parts of propionaldehyde (0.53mol) 0.2 part of a platinum oxide catalyst (prepared according to the method of Adams, Voorhees and.

shriner, Ore. Synth. VIII, 92) and 150 parts by volume of 95% alcohol was shaken in a pressure bottle under 8-50 1bs./sq. in. hydrogen pressure at room temperature. To increase the rate of hydrogenation, 0.2 part more of platinum oxide catalyst was added after 1% hours. Hydrogenatilled in vacuo. The distillate V through its neutral oxalate salt.

I aminophenol (CsHnON) is 9.26

tion was complete at the end of 37 hours. Thereduced mixture was filtered from the catalyst, and the filtrate was freed of solvent by distillation on'a steam bath under reduced pressure. The residue was slurried with 200 parts by volume of benzene, cooled and filtered from 8 parts (18.4%) of p-aminophenol. After removal. of solvent from the filtrate, the residue was disred oil, B. P. 120-149 C./0.5'mm., containing 8.05% N. A sample of the product was purified The purified neutral oxalate melted at 202-204 C. (gas evolution). ate, when converted'to the base, gave N-propylp-aminophenol as white needles, M. P. 83-85 C. containing 9.43% N. The melting point of the base was not lowered when purified sample (M. P. 88-89 C.) of N-propyl-paminophenol, prepared from p-aminophenol and propyl bromide. The theory for N-propyl-p- EXAMPLE 2 N-butyl-p-aminophenol A mixture of 139 parts of p-nitrophenol (1.0 moi), 22 parts of n-butyraldehyde (0.3 mol), 30

parts of a nickel-on-kieselguhr catalyst and 1000 parts by volume of pumped into the autoclave in 4 approximately equal portions at A hour intervals. When no further hydrogen was absorbed, the charge was cooled and filtered from the catalyst. The filtrate was freed of solvent by distillation under 200 mm. pressure, and the residue was distilled in vacuo. Thedistillate was 157 parts (95.2% theory) of a yellow oil. B. P. 120-142 C./0.5 mm, which solidified on cooling and contained 7.60% N. A sample of the distillate was purified by three crystallizations from a mixture of benzene and 30-60 C; petroleum ether. The purified material was obtained as light tan crystals, M. P. 69-70 C.,'containing 8.56% N. Its melting point mixed with a highly was 40 parts of' a A sample of the purified neutral oxal- The productwas 54 parts of a colorless oil, B. P. 130-,155.C../0.5 mm.. which promptly solidified on cooling and contained 8.38% N.

A sample of the product, crystallized from a mixture of benzene and 80-60, C. petroleum ether, melted at 77-78 C. and contained 8.45% N. Its melting point was not lowered when mixed with a highly purified sample (M. P. 79 C.) of N isobutyl p aminophenol prepared from p-aminophenolv and isobutyraldehyde. The theory for N-isobutyl-p-aminophenol (CroHuON) is 8.48% N.

Exmrm 4 N-isobutyl-p-aminophenol -A mixture of 48 parts of p-nitrosophenol (0.39 mol) 43 parts of isobutyraldehyde (0.6 mol), 0.2

. part or a platinum oxide catalyst (prepared acwas not lowered when mixed with a highly purified sample (M. P. 69-70" C.) of N-butyl-paminophenol, obtainedfrom hydroquinone and Exnrrtn 3 N-isobutyl-p-aminophenol A mixture of 56 parts of p-nitrophenol (0.4 mol), 43 parts of isobutyraldehyde (0.6 mol). 2 parts of sodiumacetate, 10 parts of a nickel-onkieselguhr catalyst and 200 parts by volume of 95% alcohol was shaken in a steel bomb at-99- 101 C. under 400-500 lbs/sq. in. hydrogenpressure. Hydrogenation required hour. The reduced mixture was cooled and filtered from the catalyst, and the filtrate was freed of solvent by distillation under 200 mm. pressure. The residual oil was slurried with200 parts by volume of benzene and filtered from 4 parts (7.7% theory) of p-aminophenol. The filtrate was freed of cording to the method of Adams, Voorhees, and

Shriner, Org. Synth. VIII, 92) and 100 parts by volume of 95% alcohol was shaken in a pressure bottle under 28-49 lbs/sq. in. hydrogen pressure at room temperature. To increase the' rate of hydrogenation, 0.2 part more of platinum oxide catalyst was added after 17 hours, and 0.4 part more of platinum oxide catalyst was added after 5 more hours. Hydrogenation was complete at the end of 38 hours. The reduced mixture was filtered from the catalyst, and the filtrate was freed of solvent by distillation on a steam bath under reduced pressure. The residue was slurried well with 500 parts by volume of warm benzene, and the mixture was cooled and decanted through a filter from some insoluble tarry material. After removing the solvent from the filtrate, the residue was distilled under reduced pressure. The distillate. was ,13 parts of an orange oil, B. P. 131- 157 C./0.5 mm. This was purified through its neutral oxalate salt. The purified neutral .oxalate melted at 179-180 C. (gas evolution), and its melting point was not lowered when mixed with a highly purified sample (M, P, 180-181" 0., gas evolution) of N -isobutyl-p-aminophenol neutral oxalate obtained from p-aminophenol and isobutyraldehyde. The purified base was obtained as light-tan plates, M. P. 78-79 C. Its melting point was not depressed when mixed with a highly purified sample (M. P. 79 C.) of N-isobutyl-p-aminophenol obtained from paminophenol and isobutyraldehyde,

solvent, and the residue was distilled in vacuo.

EXAMPLE 5 N-isobutyZ-p-aminophenol A solution of 337 parts of sodium hydroxide (8 mols) in-780 parts of water was slowly added to a mixture 01 69.5 parts of p-nitrophenol (0.5 mol), 54 parts of isobutyraldehyde (0.75 mol), and 263 parts of zinc dust (4 mols) in 1220 parts of water, with stirring at 0-5 C..during 1 hours in a vessel from which air was excluded to prevent oxidation. After stirring. at 0-5 C. for 2 hours longer, 1650 parts of concentrated hydrochloric acid (17 mols) was added, and the mixture was quickly filtered from some unreacted zinc dust. The filtrate was treated with an excess of ammonium hydroxide and extracted with 1500 parts by volume of benzene. extract was dried over sodium sulfate and freed of solvent by distillation on a steam bath under 200, mm. pressure. The residue was 38.7 parts of a red 01]. This, when purified through its neutral oxalate phenol.

It will be readily understood by those skilled in The benzene salt, yielded N-isobutyl-p-aminothe art that the above examples are given ior illustrative purposes only. Many variations and modifications can be made in the ingredients and conditions employed. For example, buiiers, such as sodium acetate or potassium acetate, may be present in the reduction mixture, although their use is not always necessary or desirable. Accordingly, the scope of my invention is not to be limited to the specific-examples given, but 1 intend to claim the invention broadly as in the appended claims.

The process oi the present invention has the advantage that it renders it possible to prepare N-alkyl aminophenols in high yields irom the relatively cheap p-nitrophenol and p-nitrosophenol, and thus avoid-the use oi the relatively expensive p-aminophenol or hydroquinone which have been more usually employed; Also, since the p-nitrophenols and the p-nitrosophenols are relat'ively more stable to oxidation and easier to handle than the p-aminophenols, iurther advantages are thus obtained.

The compounds, prepared by the process oi my invention, may be used in gasoline, iats, oils, waxes and rubber to retard or inhibit oxidation and/or gum iormation and to improve the stability oi these substances. They are particularly useiul for this purpose in motor-iuels. especially thosecontaining cracked gasoline, which may or may not contain anti-knock agents such as tetraethyl lead. Their use in petroleum oils, lubricating oils, transformer oils, over-head lubricants, extreme pressure lubricants and the like may be in conjunction with additives such as pour-point improvers, viscosity-index improvers, corrosion inhibitors, polymerization inhibitors and the like. They may be used as photographic developers and as intermediates in the preps-ration oi dyes, pharmaceuticals and cosmetics.

I claim:

1. In the preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing a member the group consisting oi pnitrophenols and p-nitrosophenolsin the pres-- ence oi an aliphatic aldehyde, containing at least 3 carbon atoms, in an inert solvent, said nitrophenols and nitrosophenols being oi the benzene series.

, 2. In the preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing a member 01 the group consisting oi pnitrophenols and p-nitrosophenols, devoid oi nonhydrocarbon substituents, in the presence oi an p-nitrophenol and p-nitrosophenol, said nitrophenols and nitrosophenols being oi the benzene series.

5. In the preparation oi p-(N-primary aliphatic amino)phenols, the processwhich comprises-reducing a member oi the group consisting oi pnitrophenols and p-nitrosophenols, devoid oi nonhydrocarbon substituents, in the presence oi an alkyl aldehyde containing irom 3 to 6 carbon atoms, in an inert solvent, employing irom about 1 to about 1.5 mols oi the aldehyde ior each moi oi p-nitrophenol and p-nitrosophenol and adding the aldehyde to the solution gradually during the course oi the reduction, said nitrophenols and nitrosophenols being oi the benzene series.

8. In the preparation oi p-(N-primary aliphatic amino) phenols, the process which comprises reducing p-nitrophenol in the presence oi an allphatic aldehyde containing at least 3 carbon atoms, in an inert solvent.

7. In the preparation oi p-(N-primary aliphatic amino) phenols, the process which comprises reducing p-nitrophenol in the presence oi an unsubstituted aliphatic aldehyde containing at least 3 carbon atoms, in an inert solvent, adding the aldehyde to the solution gradually during the course oi the reduction.

8. In the preparation oi p- (N-primary. aliphatic amino)phenols, the process which comprises reducing p-nitrophenol in the presence oi an alkyl aldehyde containing at least 3 carbon atoms, in an inert solvent, employing irom about 1 to about 1.5 mols oi the aldehyde ior each-mol oi p-nitrophenol.

9. In the preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing p-nitrophenol in the presence oi an alkyl aliphatic aldehyde, containing at least 3 carbon-- nitrophenols and nitrosophenois being oi the benzene series.

4. Inthe preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing a member oi. the group consisting oi pnitrophenols and p-nltrosophenols, devoid oi nonhydrocarbonsubstituents, in the presence oi an alkyl aldehyde containing at least 3 carbon atoms, inan inert solvent. employing irom about 1 to about 1.5 mols oi the aldehyde ior each mol oi aldehyde containing irom 3 to 6 carbon atoms, in an inert solvent, employing irom about 1 to about 1.5 mols oi the aldehyde ior each mol oi p-nitrophenol.

10. In the preparation of p-(N-isobutyl amino)phenols, the process which comprises reducing p-nitrophenol in the presence oi isobutyraldehyde, in an inert solvent,employing irom about 1 to about 1.5 mols oi the aldehyde ior eachmoi oi p-nitrophenol.

.11. In the preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing p-nitrosophenol in the presence oi an aliphatic aldehyde containing at least 3 carbon atoms, in an inert solvent.

12. In the preparation of p-(N-primary aliphatic amino) phenols, the process which comprises reducing p-nitrosophenol in the presence of an unsubstituted aliphatic aldehyde containing at least 3 carbon atoms, in an inert solvent, adding the aldehyde to the solution gradually during the course of the reduction.

13. In the preparation oi p-(N-primary aliphatic amino)phenols, the process which comprises reducing p-nitrosophenol in the presence oi an alkyl aldehyde containing from 3 to 6 carbon atoms. in an inert solvent, employing from about 1 to about 1.5 mols oi the aldehyde 1 to about is mols oi the aldehyde for each mol of p-nitropsophenol.

15. In the preparation oi a p-(N-primary aliphatic amino)phenol, the step which comprises aldehyde containing at least 3 carbon atoms, said nitrophenols and nitrosophenols being of the benzene series.

16. In the preparation of a p-(N-primary aliphatic amino)phenol, the step which comprises hydrogenating, in the presence of a hydrogenating catalyst at temperatures of from about atmospheric to about 200- C. under pressures of at least 2 atmospheres in an inert polar solvent, a member of the group consisting of p-nitrophenols and p-nitrosophenols, devoid of non-hydrocarbon substituents, in the presence oi an unsubstituted aliphatic aldehyde of from 3v to 6 carbon atoms, said nitrophenols and nitrosophenols being of the benzene series.

17. In the preparation of a p-(N-primary alinitrosophenols. devoid of non-hydrocarbon substituents, in the presence of an unsubstituted aliphatic aldehyde of from 3 to 6 carbon atoms, employing from about 1 to about 1.5 mols of the aldehyde for each mol of p-nitrophenoi and pnitrosophenol, said nitrophenols and nitrosophenols being of the benzene series.

19. In the preparation of a p w-primary aliphatic amino) phenol, the step which comprises hydrogenating, in the presence of a hydrogenating catalyst at temperatures of from about atmospheric to about 200 C. under pressures of at least 2 atmospheres in an inert solvent, a memphatic -amino)phenol, the step which comprises hydrogenating, in the presence of a hydrogenating catalyst at temperatures or from about atmospheric to about 200 C. under pressures of at least 2 atmospheres in an inert alcoholic solution, a member of the group consisting of]:- nitrophenols and p-nitrosophenols, devoid of nonhydrocarbon substituents, in the presence oi an unsubstituted aliphatic aldehyde of from 3 to 6 carbon atoms, employing from about 1 to about 1.5 mols of the aldehyde for each moi of pnitrophenol and p-nitrosophenol, said nitrophenols and nitrosophenols being of the benzene ser es.

18. In the preparation of a p-.(N-primary aliphatic amino)phenoi, the step which comprises hydrogenating, in the presence of a hydrogenating catalyst at temperatures of from about atmospheric to about 200 C. under pressures of at least 2 atmospheres in 95% alcohol, a member of the group consisting of p-nitrophenols and pber of the group consisting of p-nitrophenols and p-nitr'osophenols in the presence of an aliphatic aldehyde containing at least 3 .carbon atoms, adding the aldehyde to the solution gradually during the course of the hydrogenation, saidv nitrophenols andnitrosophenols being of the benzene series.

20. In the preparation of a p-(N-primary aliphatic amino)phenol, the step which comprises hydrogenating, in the presence of a hydrogenating catalyst at temperatures of from about C. to about 150 C. under pressures of from about 2 to about atmospheres in an inert alcoholic solution, a member of the group consisting of penitrophenols and p-nitrosophenols, devoid of non-hydrocarbon substituents, in the presence of an unsubstituted aliphatic aldehyde of from 3 to 6 carbon atoms, employing from about.1 to about 1.5 mols of the aldehyde for each moi of p-nitrophenol and p-nitrosophenol and adding the aldehyde to the solution gradually during the course of the hydrogenation, said nitrophenols and nitrosophenols being of the benzene series.

'21. In the preparation of p-(N-butylamino) phenols, the process which comprises reducing -p-nitrophenol in the presence of butyraldehyde, in an inert solvent, employing from about 1 to about 1.5 mols of the butyraldehyde for each mol of p-nitrophenol.

HOWARD M. FITCH. 

